Screening of food factors that target the quality control system of mitochondria

• Project/Area Number: 23658118
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Food science
• Research Institution: Nagoya University
• Principal Investigator: KAWAI Yoshichika 名古屋大学, 生命農学研究科, 准教授 (50380027)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: オートファジー / ポリフェノール / フラボノイド / ミトコンドリア / マクロファージ / 炎症 / 食品因子

Research Abstract

We screened the food factors that enhance the autophagic degradation leading to mitochondrial quality control. In HeLa cells, luteolin and the derivatives significantly enhanced the autophagic degradation of p62, an adaptor protein of autophagy. In contrast, in J774.1 macrophages, the mRNA expression of p62 was significantly enhanced upon treatment with flavonols such as quercetin, whereas no effects were observed upon treatment with luteolin derivatives. These results strongly suggest that the activities of polyphenols for autophagy induction are dependent on cell types. It was also found that p62 mRNA expression was enhanced through the activation of Nrf2, a transcription factor. Furthermore, the pretreatment of J774.1 with flavonols resulted in the decrease in both intracellular and extracellular IL-1beta, an autophagy substrate. These results suggest that autophagy induction by polyphenols might be good strategy for the quality control of intracellular proteins and organelles.

Research Products

• [Journal Article] Mitochondrial dysfunction leads to deconjugation of quercetin glucuronides in inflammatory macrophages (2013)
  • Author(s): Ishisaka, A., Kawabata, K., Miki, S., Shiba, Y., Minekawa, S., Nishikawa, T., Mukai, R., Terao, J., and Kawai, Y
  • Journal Title: PLoS One Volume: 8 Issue: 11 Pages: e80843-e80843
  • DOI: 10.1371/journal.pone.0080843
  • Peer Reviewed
• [Journal Article] Non-specific protein modifications by a phytochemical induce heat shock response for self-defense (2013)
  • Author(s): Kohta Ohnishi
  • Journal Title: PLoS One Volume: 8(3) Issue: 3 Pages: 1-15
  • DOI: 10.1371/journal.pone.0058641
  • Peer Reviewed / Open Access
• [Journal Article] Atg7 modulates p53 activity to regulate cell cycle and survival during metabolic stress (2012)
  • Author(s): Lee, I.H., Kawai, Y., Fergusson, M.M., Rovira, I.I., Bishop, A.J., Motoyama, N., Cao, L., and Finkel, T
  • Journal Title: Science Volume: 336 Issue: 6078 Pages: 225-228
  • DOI: 10.1126/science.1218395
  • Peer Reviewed
• [Journal Article] Bioavailability of orally administered water-dispersible hesperetin and its effect on peripheral vasodilatation in human subjects: implication of endothelial functions of plasma conjugated metabolites. (2012)
  • Author(s): Takumi, H., Nakamura, H., Simizu, T., Harada, R., Kometani, T., Nadamoto, T., Mukai, R., Murota, K., Kawai, Y., and Terao, J.
  • Journal Title: Food and Function Volume: 3 Issue: 4 Pages: 389-398
  • DOI: 10.1039/c2fo10224b
  • Peer Reviewed
• [Journal Article] Effect of quercetin and its glucuronide metabolite upon 6-hydorxydopamine-induced oxidative damage in Neuro-2a cells. (2012)
  • Author(s): Mukai, R., Kawabata, K., Otsuka, S., Ishisaka, A., Kawai, Y., Ji, Z.S., Tsuboi, H., and Terao, J.
  • Journal Title: Free Radical Research Volume: 46 Issue: 8 Pages: 1019-1028
  • DOI: 10.3109/10715762.2012.673720
  • Peer Reviewed
• [Journal Article] Monoclonal antibody against protein-bound glutathione: use of glutathione conjugate of acrolein-modified proteins as an immunogen. (2012)
  • Author(s): Furuhata, A., Honda, K., Shibata, T., Chikazawa, M., Kawai, Y., Shibata, N., and Uchida, K.
  • Journal Title: Chemical Research in Toxicology Volume: 25 Issue: 7 Pages: 1392-1401
  • DOI: 10.1021/tx300082u
  • Peer Reviewed
• [Journal Article] Quantitative analysis of acrolein-specific adducts generated during lipid peroxidation-modification of proteins in vitro: identification of N(τ)-(3-propanal)histidine as the major adduct. (2012)
  • Author(s): Maeshima, T., Honda, K., Chikazawa, M., Shibata, T., Kawai, Y., Akagawa, M., and Uchida, K.
  • Journal Title: Chemical Research in Toxicology Volume: 25 Issue: 7 Pages: 1384-1392
  • DOI: 10.1021/tx3000818
  • Peer Reviewed
• [Journal Article] The ferroimmunomodulatory role of ectopic endometriotic stromal cells in ovarian endometriosis. (2012)
  • Author(s): Kobayashi H, Yamashita Y, Iwase A, Yoshikawa Y, Yasui H, Kawai Y, Uchida K, Uno N, Akatsuka S, Takahashi T, Kikkawa F, Toyokuni S.
  • Journal Title: Fertil Steril Volume: 98 Issue: 2 Pages: 415-22
  • DOI: 10.1016/j.fertnstert.2012.04.047
  • Peer Reviewed
• [Journal Article] Effect of quercetin and glucuronide metabolites on the monoamine oxidase-A reaction in mouse brain mitochondria (2011)
  • Author(s): Yoshino, S., Hara, A., Sakakibara, H., Kawabata, K., Tokumura, A., Ishisaka, A., Kawai, Y., and Terao, J.
  • Journal Title: Nutrition Volume: 27 Pages: 847-852
  • Peer Reviewed
• [Journal Article] Pharmacology in health food: metabolism of quercetin in vivo and its protective effect against arteriosclerosis (2011)
  • Author(s): Ishizawa, K., Yoshizumi, M., Kawai, Y., Terao, J., Kihira, Y., Ikeda, Y., Tomita, S., Minakuchi, K., Tsuchiya, K., and Tamaki, T.
  • Journal Title: Journal of Pharmacological Sciences Volume: 115 Pages: 466-470
  • NAID: 10029893264
  • Peer Reviewed
• [Journal Article] Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats. (2011)
  • Author(s): Ishisaka, A., Ichikawa, S., Sakakibara, H., Piskula, M.K., Nakamura, T., Kato, Y., Ito, M., Miyamoto, K., Tsuji, A., Kawai, Y., and Terao, J.
  • Journal Title: Free Radical Biology and Medicine Volume: 51 Pages: 1329-1336
  • Peer Reviewed
• [Journal Article] Benzene Metabolite, 1,2,4-benzenetriol, induces halogenated DNA and tyrosines representing halogenative stress in human myeloid cell line HL-60. (2011)
  • Author(s): Nishikawa, T., Miyahara, E., Horiuchi, M., Izumo, K., Okamoto, Y., Kawai, Y., Kawano, Y., Takeuchi, T.
  • Journal Title: Environmental Health Perspectives Volume: 120 Pages: 62-67
  • Peer Reviewed
• [Journal Article] Immunochemical Detection of Food-Derived Polyphenols in the Aorta: Macrophages as a Major Target Underlying the Anti-Atherosclerotic Activity of Polyphenols. (2011)
  • Author(s): Kawai, Y.
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: 75 Pages: 609-617
  • NAID: 10028271026
• [Journal Article] Conjugated quercetin glucuronides as bioactive metabolites and precursors of aglycone in vivo. (2011)
  • Author(s): Terao, J., Murota, K., and Kawai, Y.
  • Journal Title: Food and Function Volume: 2 Pages: 11-7
• [Presentation] マクロファージとの相互作用を介したポリフェノール抱合体の活性制御機構 (2013)
  • Author(s): 河合慶親
  • Organizer: 第67回日本栄養・食糧学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2013-05-25
• [Presentation] Flavonoids induce autophagic degradation : a possible mechanism for the health-beneficial effects of dietary flavonoids (2013)
  • Author(s): Yoshichika Kawai
  • Organizer: 13th International Conference of Functional Food Center (FFC)
  • Place of Presentation: Kyoto(シンポジウム講演)
  • Year and Date: 2013-05-11
• [Presentation] オートファジー誘導を介した抗炎症作用を有するポリフェノール類の探索 (2013)
  • Author(s): 坂下 友紀、額 惠理香、大西 康太、河合 慶親
  • Organizer: 第18回日本フードファクター学会（JSoFF）
  • Place of Presentation: 東京
• [Presentation] Flavonoids induce autophagic degradation: a possible mechanism for the health-beneficial effects of dietary flavonoids (2013)
  • Author(s): Yoshichika Kawai
  • Organizer: 13th International Conference of Functional Food Center (FFC)
  • Place of Presentation: 京都
  • Invited
• [Presentation] New insights into the anti-inflammatory mechanisms of dietary flavonoids: involvement of mitochondrial dysfunction and autophagy (2013)
  • Author(s): Yoshichika Kawai
  • Organizer: 6th International conference on Polyphenol and Health (ICPH)
  • Place of Presentation: ブエノスアイレス
  • Invited
• [Presentation] LC-MS/MSによる過酸化脂質－DNA付加体の網羅解析及び検出系の確立 (2013)
  • Author(s): 河合慶親、額惠理香、柴田貴広、内田浩二
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 仙台
• [Presentation] ミトコンドリア障害に起因するマクロファージ炎症応答機構の解析 (2012)
  • Author(s): 河合慶親, 川津英賢, 柴田貴広, 内田浩二
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 博多
  • Year and Date: 2012-12-15
• [Presentation] フラボノイド類によるオートファジー誘導機構の解析 (2012)
  • Author(s): 石原朋恵, 寺尾純二, 柴田貴広, 内田浩二, 河合慶親
  • Organizer: 2012年度日本農芸化学会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-23
• [Presentation] 炎症部位における抗酸化ポリフェノールの機能性発現機構の解析 (2012)
  • Author(s): 河合慶親
  • Organizer: 日本酸化ストレス学会東海支部設立シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2012-02-18
• [Presentation] フラボノイド類によるオートファジー誘導機構の解析 (2012)
  • Author(s): 石原朋恵、寺尾純二、柴田貴広、内田浩二、河合慶親:
  • Organizer: 日本農芸化学会2012年度大会
  • Place of Presentation: 京都女子大学（京都）
• [Presentation] マクロファージにおけるポリフェノールの抗炎症作用機構の解析 (2012)
  • Author(s): 神原哲士、河合慶親、柴田貴広、内田浩二:
  • Organizer: 日本農芸化学会2012年度大会
  • Place of Presentation: 京都女子大学（京都）
• [Presentation] 炎症部位における抗酸化ポリフェノールの機能性発現機構の解析 (2012)
  • Author(s): 河合慶親
  • Organizer: 日本酸化ストレス学会東海支部設立シンポジウム(招待講演)
  • Place of Presentation: 名古屋大学医学部（名古屋）
• [Presentation] Prodrug-like actions of dietary polyphenols at the sites of inflammation (2012)
  • Author(s): Kawai, Y
  • Organizer: The International Symposium on Food, Nutrition, and Vascular Function 2012(招待講演)
  • Place of Presentation: 徳島大学（徳島）
• [Presentation] Toren Finkel : ミトコンドリア膜電位低下に伴うLC3-PE 複合体生成機構の解析 (2011)
  • Author(s): 河合慶親, 柴田貴広, 内田浩二
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-24
• [Presentation] ミトコンドリア膜電位低下に伴うLC3-PE複合体生成機構の解析 (2011)
  • Author(s): 河合慶親、柴田貴広、内田浩二、Toren Finkel
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都国際会館（京都）
• [Remarks]
  • URL: http://www.agr.nagoya-u.ac.jp/~food/
• [Remarks] 名古屋大学大学院生命農学研究科食品機能化学研究室
  • URL: http://www.agr.nagoya-u.ac.jp/~food/index.html
• [Remarks]
  • URL: http://www.agr.nagoya-u.ac.jp/~food/index.html